Selenocysteine: Difference between revisions

Selenocysteine^[1]
Names
	IUPAC name 3-Selanyl-2-aminopropanoic acid
	Other names L-Selenocysteine; 3-Selanyl-L-alanine; Selenium cysteine
Identifiers
CAS Number	10236-58-5 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:16633 ;
ChEMBL	ChEMBL109962 ;
ChemSpider	23436 ;
DrugBank	DB02345 ;
ECHA InfoCard	100.236.386
KEGG	C05688 ;
PubChem CID	25076;
CompTox Dashboard (EPA)	DTXSID00881371 ;
	InChI InChI=1S/C3H7NO2Se/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1 Key: ZKZBPNGNEQAJSX-REOHCLBHSA-N ; InChI=1/C3H7NO2Se/c4-2(1-7)3(5)6/h2,7H,1,4H2,(H,5,6)/t2-/m0/s1 Key: ZKZBPNGNEQAJSX-REOHCLBHBZ;
	SMILES O=C(O)[C@@H](N)C[SeH];
Properties
Chemical formula	C3H7NO2Se
Molar mass	168.065 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

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Selenocysteine (abbreviated as Sec or U, in older publications also as Se-Cys)^[2] is considered to be the 21st proteinogenic amino acid. It exists naturally in all kingdoms of life as a building block of selenoproteins.^[3] Selenocysteine is a cysteine analogue with a selenium-containing selenol group in place of the sulfur-containing thiol group. Selenocysteine is present in several enzymes (for example glutathione peroxidases, tetraiodothyronine 5' deiodinases, thioredoxin reductases, formate dehydrogenases, glycine reductases, selenophosphate synthetase 1, methionine-R-sulfoxide reductase B1 (SEPX1), and some hydrogenases).

Structure

Selenocysteine has a structure similar to that of cysteine, but with an atom of selenium taking the place of the usual sulfur, forming a selenol group which is deprotonated at physiological pH. Proteins that contain one or more selenocysteine residues are called selenoproteins.

Biology

Selenocysteine has both a lower pKa (5.47) and a higher reduction potential than cysteine. These properties make it very suitable in proteins that are involved in anti-oxidant activity.^[4]

Unlike other amino acids present in biological proteins, selenocysteine is not coded for directly in the genetic code.^[5] Instead, it is encoded in a special way by a UGA codon, which is normally a stop codon. Such a mechanism is called translational recoding^[6] and its efficiency depends on the selenoprotein being synthesized and on translation initiation factors.^[7] When cells are grown in the absence of selenium, translation of selenoproteins terminates at the UGA codon, resulting in a truncated, nonfunctional enzyme. The UGA codon is made to encode selenocysteine by the presence of a SECIS element (SElenoCysteine Insertion Sequence) in the mRNA. The SECIS element is defined by characteristic nucleotide sequences and secondary structure base-pairing patterns. In bacteria, the SECIS element is typically located immediately following the UGA codon within the reading frame for the selenoprotein.^[8] In archaea and in eukaryotes, the SECIS element is in the 3' untranslated region (3' UTR) of the mRNA, and can direct multiple UGA codons to encode selenocysteine residues.^[9]

Again unlike the other amino acids, no free pool of selenocysteine exists in the cell. Its high reactivity would incur damage to cells. Instead, cells store selenium in the less reactive selenide form (H₂Se). Selenocysteine synthesis occurs on a specialized tRNA, which also functions to incorporate it into nascent polypeptides. The primary and secondary structure of selenocysteine tRNA, tRNA(Sec), differ from those of standard tRNAs in several respects, most notably in having an 8-base (bacteria) or 10-base (eukaryotes) pair acceptor stem, a long variable region arm, and substitutions at several well-conserved base positions. The selenocysteine tRNAs are initially charged with serine by seryl-tRNA ligase, but the resulting Ser-tRNA(Sec) is not used for translation because it is not recognised by the normal translation factor (EF-Tu in bacteria, eEF1A in eukaryotes). Rather, the tRNA-bound seryl residue is converted to a selenocysteine-residue by the pyridoxal phosphate-containing enzyme selenocysteine synthase. Finally, the resulting Sec-tRNA(Sec) is specifically bound to an alternative translational elongation factor (SelB or mSelB (a.k.a. eEFSec)), which delivers it in a targeted manner to the ribosomes translating mRNAs for selenoproteins. The specificity of this delivery mechanism is brought about by the presence of an extra protein domain (in bacteria, SelB) or an extra subunit (SBP2 for eukaryotic mSelB/eEFSec) which bind to the corresponding RNA secondary structures formed by the SECIS elements in selenoprotein mRNAs.

There are 25 human proteins that contain selenocysteine (selenoproteins).^[10]

Selenocysteine derivatives γ-glutamyl-Se-methylselenocysteine and Se-methylselenocysteine occur naturally in genus Allium and Brassica plants.^[11]

Applications

Biotechnological applications of selenocysteine include use of ⁷³Se-labeled Sec (half-life of ⁷³Se = 7.2 hours) in positron emission tomography (PET) studies and ⁷⁵Se-labeled Sec (half-life of ⁷³Se = 118.5 days) in specific radiolabeling, facilitation of phase determination by multi-wavelength anomalous diffraction in X-ray crystallography of proteins by introducing Sec alone, or Sec together with selenomethionine (SeMet), and incorporation of the stable ⁷⁷Se isotope, which has a nuclear spin of 1/2 and can be used for high-resolution NMR, among others.Cite error: The opening <ref> tag is malformed or has a bad name (see the help page).

References

^ Merck Index, 12th Edition, 8584
^ "IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature Committee of IUBMB (NC-IUBMB)" (pdf). European Journal of Biochemistry. 264 (2): 607–609. 1999. doi:10.1046/j.1432-1327.1999.news99.x.
^ Johansson, L.; Gafvelin, G.; Amér, E. S. J. (2005). "Selenocysteine in Proteins — Properties and Biotechnological Use". Biochimica et Biophysica Acta. 1726 (1): 1–13. doi:10.1016/j.bbagen.2005.05.010.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Byun, B. J.; Kang, Y. K. (2011). "Conformational Preferences and pK_a Value of Selenocysteine Residue". Biopolymers. 95 (5): 345–353. doi:10.1002/bip.21581. PMID 21213257.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Böck A.; Forchhammer, K.; Heider, J.; Baron, C. (1991). "Selenoprotein Synthesis: An Expansion of the Genetic Code". Trends in Biochemical Sciences. 16 (12): 463–467. doi:10.1016/0968-0004(91)90180-4. PMID 1838215.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Baranov P. V.; Gesteland R. F.; Atkins, J. F. (2002). "Recoding: Translational Bifurcations in Gene Expression". Gene. 286 (5): 187–201. doi:10.1016/S0378-1119(02)00423-7. PMID 11943474.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Donovan, J.; Copeland, P. R. (2010). "The Efficiency of Selenocysteine Incorporation is Regulated by Translation Initiation Factors". Journal of Molecular Biology. 400 (4): 659–664. doi:10.1016/j.jmb.2010.05.026. PMID 20488192.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Atkins, J. F. (2009). Recoding: Expansion of Decoding Rules Enriches Gene Expression. Springer. p. 31. ISBN 9780387893815.
^ Berry, M. J.; Banu, L.; Harney, J. W.; Larsen, P. R. (1993). "Functional Characterization of the Eukaryotic SECIS Elements which Direct Selenocysteine Insertion at UGA Codons" (pdf). The EMBO Journal. 12 (8): 3315–3322. PMC 413599. PMID 8344267.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Kryukov, G. V.; Castellano, S.; Novoselov, S. V.; Lobanov, A. V.; Zehtab, O.; Guigó, R.; Gladyshev, V. N. (2003). "Characterization of Mammalian Selenoproteomes". Science. 300 (5624): 1439–1443. doi:10.1126/science.1083516. PMID 12775843.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Block, E. (2010). Garlic and Other Alliums: The Lore and the Science. Royal Society of Chemistry. ISBN 0-85404-190-7.

@@ Line 53: / Line 53: @@
 Selenocysteine has both a lower pKa (5.47) and a higher reduction potential than cysteine.  These properties make it very suitable in proteins that are involved in anti-oxidant activity.<ref>{{ cite journal | author = Byun, B. J.; Kang, Y. K. | title = Conformational Preferences and pK<sub>a</sub> Value of Selenocysteine Residue | journal = [[Biopolymers]] | year = 2011 | volume = 95 | issue = 5 | pages = 345–353 | doi =  10.1002/bip.21581 | pmid = 21213257 }} </ref>
-Unlike other amino acids present in biological [[protein]]s, selenocysteine is not coded for directly in the [[genetic code]].<ref> {{ cite journal | author = Böck A.; Forchhammer, K.; Heider, J.; Baron, C. | title = Selenoprotein Synthesis: An Expansion of the Genetic Code | journal = [[Trends in Biochemical Sciences]] | year = 1991 | volume = 16 | issue = 12 | pages = 463–467 | pmid = 1838215 | doi = 10.1016/0968-0004(91)90180-4 }}</ref> Instead, it is encoded in a special way by a UGA [[codon]], which is normally a stop codon. Such a mechanism is called translational recoding<ref>{{ cite journal | author = Baranov P. V.; Gesteland R. F.; Atkins, J. F. | title = Recoding: Translational Bifurcations in Gene Expression | journal = Gene | year = 2002 | volume = 286 | issue = 5 | pages = 187–201 | doi =  10.1016/S0378-1119(02)00423-7 | pmid = 11943474 }}</ref> and its efficiency depends on the selenoprotein being synthesized and on translation initiation factors.<ref>{{ cite journal | author = Donovan, J.; Copeland, P. R. | title = The Efficiency of Selenocysteine Incorporation is Regulated by Translation Initiation Factors  | journal = [[Journal of Molecular Biology]] | year = 2010 | volume = 400 | issue = 4 | pages = 659–664 | pmid =  20488192 | doi = 10.1016/j.jmb.2010.05.026 }}</ref> When cells are grown in the absence of selenium, translation of selenoproteins terminates at the UGA codon, resulting in a truncated, nonfunctional enzyme. The UGA codon is made to encode selenocysteine by the presence of a [[SECIS element]] (SElenoCysteine Insertion Sequence) in the [[mRNA]].  The SECIS element is defined by characteristic nucleotide sequences and secondary structure base-pairing patterns.  In [[bacteria]], the SECIS element is typically located immediately following the UGA codon within the reading frame for the selenoprotein.<ref>{{ cite book | author = Atkins, J. F. | title = Recoding: Expansion of Decoding Rules Enriches Gene Expression | year = 2009 | page = 31 | publisher = Springer | isbn = 9780387893815 | url = http://books.google.fr/books?id=8cSZpPWXoqIC&pg=PA31 }}</ref> In [[archaea]] and in [[eukaryote]]s, the SECIS element is in the [[3' UTR|3' untranslated region]] (3' UTR) of the mRNA, and can direct multiple UGA codons to encode selenocysteine residues.<ref> {{ cite journal | author = Berry, M. J.; Banu, L.; Harney, J. W.; Larsen, P. R. | title = Functional Characterization of the Eukaryotic SECIS Elements which Direct Selenocysteine Insertion at UGA Codons | journal = [[The EMBO Journal]] | year = 1993 | volume = 12 | issue = 8 | pages = 3315–3322 | pmid = 8344267 | pmc = 413599 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC413599/pdf/emboj00080-0320.pdf | format = pdf }} </ref>
+Unlike other amino acids present in biological [[protein]]s, selenocysteine is not coded for directly in the [[genetic code]].<ref> {{ cite journal | author = Böck A.; Forchhammer, K.; Heider, J.; Baron, C. | title = Selenoprotein Synthesis: An Expansion of the Genetic Code | journal = [[Trends in Biochemical Sciences]] | year = 1991 | volume = 16 | issue = 12 | pages = 463–467 | pmid = 1838215 | doi = 10.1016/0968-0004(91)90180-4 }}</ref> Instead, it is encoded in a special way by a UGA [[codon]], which is normally a stop codon. Such a mechanism is called translational recoding<ref>{{ cite journal | author = Baranov P. V.; Gesteland R. F.; Atkins, J. F. | title = Recoding: Translational Bifurcations in Gene Expression | journal = Gene | year = 2002 | volume = 286 | issue = 5 | pages = 187–201 | doi =  10.1016/S0378-1119(02)00423-7 | pmid = 11943474 }}</ref> and its efficiency depends on the selenoprotein being synthesized and on translation [[initiation factor]]s.<ref>{{ cite journal | author = Donovan, J.; Copeland, P. R. | title = The Efficiency of Selenocysteine Incorporation is Regulated by Translation Initiation Factors  | journal = [[Journal of Molecular Biology]] | year = 2010 | volume = 400 | issue = 4 | pages = 659–664 | pmid =  20488192 | doi = 10.1016/j.jmb.2010.05.026 }}</ref> When cells are grown in the absence of selenium, translation of selenoproteins terminates at the UGA codon, resulting in a truncated, nonfunctional enzyme. The UGA codon is made to encode selenocysteine by the presence of a [[SECIS element]] (SElenoCysteine Insertion Sequence) in the [[mRNA]].  The SECIS element is defined by characteristic nucleotide sequences and secondary structure base-pairing patterns.  In [[bacteria]], the SECIS element is typically located immediately following the UGA codon within the reading frame for the selenoprotein.<ref>{{ cite book | author = Atkins, J. F. | title = Recoding: Expansion of Decoding Rules Enriches Gene Expression | year = 2009 | page = 31 | publisher = Springer | isbn = 9780387893815 | url = http://books.google.fr/books?id=8cSZpPWXoqIC&pg=PA31 }}</ref> In [[archaea]] and in [[eukaryote]]s, the SECIS element is in the [[3' UTR|3' untranslated region]] (3' UTR) of the mRNA, and can direct multiple UGA codons to encode selenocysteine residues.<ref> {{ cite journal | author = Berry, M. J.; Banu, L.; Harney, J. W.; Larsen, P. R. | title = Functional Characterization of the Eukaryotic SECIS Elements which Direct Selenocysteine Insertion at UGA Codons | journal = [[The EMBO Journal]] | year = 1993 | volume = 12 | issue = 8 | pages = 3315–3322 | pmid = 8344267 | pmc = 413599 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC413599/pdf/emboj00080-0320.pdf | format = pdf }} </ref>
 Again unlike the other amino acids, no free pool of selenocysteine exists in the cell.  Its high reactivity would incur damage to cells. Instead, cells store [[selenium]] in the less reactive selenide form (H<sub>2</sub>Se).  Selenocysteine synthesis occurs on a specialized  [[tRNA]], which also functions to incorporate it into nascent polypeptides.  The primary and secondary structure of selenocysteine tRNA, tRNA(Sec), differ from those of standard tRNAs in several respects, most notably in having an 8-base (bacteria) or 10-base (eukaryotes) pair acceptor stem, a long variable region arm, and substitutions at several well-conserved base positions. The selenocysteine tRNAs are initially charged with serine by seryl-tRNA ligase, but the resulting Ser-tRNA(Sec) is not used for translation because it is not recognised by the normal translation factor (EF-Tu in bacteria, eEF1A in eukaryotes). Rather, the tRNA-bound seryl residue is converted to a selenocysteine-residue by the [[pyridoxal phosphate]]-containing enzyme selenocysteine synthase. Finally, the resulting Sec-tRNA(Sec) is specifically bound to an alternative translational elongation factor (SelB or mSelB (a.k.a. eEFSec)), which delivers it in a targeted manner to the ribosomes translating mRNAs for selenoproteins. The specificity of this delivery mechanism is brought about by the presence of an extra protein domain (in bacteria, SelB) or an extra subunit (SBP2 for eukaryotic mSelB/eEFSec) which bind to the corresponding RNA secondary structures formed by the SECIS elements in selenoprotein mRNAs.